Novel Unified Theory of Depression Points to Potential New Treatments

Progress in research on depression has been hampered by disarray among theories about the nature of the condition. In a recently published article, two neurobiologists presented a novel theory that integrates these contradictory accounts. Built on findings from a wide range of research, the theory not only reconciles disparate views of depression, but suggests possible new ways to treat it.

The researchers’ synthesis suggests that depression may be an inflammatory condition of the brain and their findings indicate that current FDA-approved anti-inflammatory drugs could be an effective treatment.

Depression is projected to become the second biggest contributor to the global burden of disease and disability by the year 2020.

Currently available antidepressant treatments provide inadequate relief for many sufferers. Roughly 15% of adult US residents have experienced a Major Depressive Episode. While the average duration of symptoms is 3 – 4 months, approximately 20% of depressive episodes run a chronic course lasting two years or longer.

What would cause the brain to become inflamed in the first place? According to the new theory, severe stress and adverse life events, such as losing a job or family member, prompt neurobiological processes that physically alter the brain by activating the inflammatory system which was designed by nature to repair tissue injury.

“It’s necessary and normal so that an individual can adapt, change behavior and deal with altered circumstances,” says Athina Markou PhD, Professor of Psychiatry at University of California, San Diego and coauthor on the study. Real problems occur only “when these restructuring processes go into overdrive, beyond what is necessary, derailing into a chronic inflammatory condition.

In addition to anti-inflammatory drugs, the theory points to another class of drugs to try in depression. We are all familiar with the soreness of a bruise or the sensitivity of a burn. That hypersensitivity to pain, or “hyperalgesia”, is triggered by our own inflammatory processes. The new theory argues that in depression, the repair of the stress-induced microdamage in the brain induces hypersensitivity to psychological pain, or “emotional hyperalgesia” if you will. A shared mechanism for physical and psychological pain means that pain killers like opiates might be effective in depression. Several small trials with depressed patients have already been published that support this possibility, though Markou cautioned that much more specific research and larger clinical trials are required.

It seems that no illness is as contentious as depression, with prescription weilding psychiatrists being accused of medicalizing normal human experience, and psychotherapists accused of romanticizing depression. The biomedical view of depression as a chemical imbalance doesn’t jibe with evolutionary psychology arguments that depression has features of an evolved adaptation.

“One thing I’m excited about is that our theory provides a way to reconcile all these conflicting views of depression” said Wager-Smith. “Because our theory proposes that a well-functioning depressive episode accomplishes an adaptive neural remodeling, it is consistent with evolutionary psychology views. It also provides a neural basis for the psychological transformation noted to occur across a depressive episode in classic psychoanalytic observations. At the same time, because we argue that the process is prone to malfunction, the theory incorporates the observation from psychiatry that depression often develops into a full-blown maladjusted pathology.”

The report was published in the journal, Neuroscience and Biobehavioral Reviews.